Blood Will Tell

Date:
11 February 2022

Pioneered at The Royal Marsden NHS Foundation Trust, with support from the NIHR BRC at The Royal Marsden and ICR, liquid biopsies allow clinicians at The Royal Marsden to personalise treatments for a range of cancers and spot recurring disease sooner using a simple blood test. 

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A photo of Professor Sanjay Popat (left) and Dr Naureen Starling (right).
Pictured: Professor Sanjay Popat (left) and Dr Naureen Starling (right)

Over the past five years, the development of liquid biopsies at The Royal Marsden and The Institute of Cancer Research, London, has provided clinicians at The Royal Marsden with an innovative new tool that allows them to tailor cancer treatments and detect relapse in patients before they experience symptoms.

Experts at the Trust are increasingly using the technique for patients at various stages in their treatment and for different cancer types, including breast, lung and colorectal. It is now being trialled to assess whether therapeutic treatments are effective and to improve patient diagnosis.

Liquid biopsies involve analysing blood samples to detect small fragments of genetic material that tumours release into the bloodstream, known as circulating tumour DNA (ctDNA). When tested in at The Royal Marsden's Centre for Molecular Pathology (CMP), a sample can tell clinicans at an earlier stage if a patient is relapsing, and can identify genetic mutations that could open up new options for targeted therapy.

Revealing relapse

“We can spot breast cancer relapse about a year before it shows up on a scan”

The Royal Marsden and The Institute of Cancer Research (ICR) became one of the early pioneers of liquid biopsies when it designed the test that was used in one of the UK’s first clinical trials of the technique.

With support from the NIHR BRC at The Royal Marsden and ICR, the plasmaMATCH trial, a Cancer Research UK funded trial led by Professor Nicholas Turner and coordinated by the ICR's Clinical Trials and Statistics Unit, examined if ctDNA testing could reveal relapses in breast cancer patients, and laid the foundations for The Royal Marsden to use liquid biopsies in other tumour types. The research also enabled the Trust to use the test to determine whether a patient is responding to treatment, as well as in place of an invasive biopsy procedure as a kinder method of diagnosing cancer.

Professor Turner, an Academic Consultant Medical Oncologist at the ICR and the Genotypes, Phenotypes and Cancer Evolution Theme Lead at the NIHR BRC at The Royal Marsden and ICR, says:

“We know from earlier clinical studies that we can find detectable ctDNA in most patients with breast cancer and identify those who will relapse about a year before it shows up on a scan.

“Technological advances over the years have meant that even though a patient may have very low levels of ctDNA, we can use this test to identify mutations in the cancer, giving us the option to use targeted therapies. The next question for us to answer is, can early detection of relapse improve patient outcomes by starting treatment early to try and prevent clinical relapse?

“We are also due to open the TRAK-ER randomised trial that uses ctDNA to detect the risk of relapse for patients with ER-positive, HER2-negative breast cancer, who receive hormone therapy for five years following treatment as standard care. There is currently no test available to tell us who will relapse in this group of patients, so ctDNA may offer us a new way of monitoring them in the future.”

Targeting lung treatment

The emergence of ctDNA testing has challenged the traditional ‘one size fits all’ approach to treating several cancer types. Liquid biopsies provide clinicians with crucial molecular information to help them tailor treatment without requiring patients to undergo invasive procedures to extract tissue biopsies.

According to Professor Sanjay Popat, Consultant Thoracic Medical Oncologist at The Royal Marsden, ctDNA testing is a quicker and more effective way to identify mutation targets than standard tissue biopsies in patients with non-small-cell lung cancer.

“All our new patients have ctDNA tests when they are referred to us, so we can either enrol them onto the Lung Unit’s wide portfolio of clinical trials of targeted therapies or start standard treatment quickly,” he says.

“The potential for using ctDNA testing for screening and diagnosing patients in the future is exciting. A blood test could simplify the diagnostic process for lung cancer, as lung tumours are often difficult to reach and identify with a bronchoscopy or biopsy. It could also speed up diagnosis, as a blood test is much more straightforward than the standard diagnostic tests based on cancer tissue.”

Sparing chemotherapy

“Thousands of bowel cancer patients a year could avoid chemotherapy”

The Royal Marsden’s TRACC study, led by Professor David Cunningham, Director of Clinical Research and Development at The Royal Marsden and Gastrointestinal Cancers Theme Lead at the NIHR BRC at The Royal Marsden, is looking into whether liquid biopsies could determine which bowel cancer patients need to undergo chemotherapy after surgery.

“We know that half of patients with high-risk stage 2 and 3 bowel cancer are cured from surgery alone, but nearly all are offered chemotherapy,” says Dr Naureen Starling, Consultant Medical Oncologist at The Royal Marsden.

“Most of our patients opt for chemotherapy as they are worried their cancer will return.

“We hope that by looking for ctDNA following surgery, we can avoid patients having chemotherapy if we don’t detect residual disease. This could transform treatment for operable bowel cancer within the next five years, meaning thousands of patients in the UK are spared unnecessary chemotherapy and its side effects every year.

“We’re also using ctDNA techniques in the PREVAIL trial to see if we can accurately diagnose patients with signs and symptoms of pancreatic, bile duct, bladder, colorectal, gastrointestinal stromal, or recurrent, difficult-to-biopsy breast cancers. These approaches could revolutionise the way we diagnose, treat and screen our patients in the future.”

Genotypes, Phenotypes and Cancer Evolution

Our vision is to improve patient outcome through precisely defining when, who and how to treat those with cancer through the use of molecular diagnostics and analytic techniques.